α-defensin 1-3 and α-defensin 4 as predictive markers of imatinib resistance and relapse in CML patients

Article type: Research Article

Authors: Etienne, Gabriel^; | Dupouy, Maryse | Costaglioli, Patricia | Chollet, Claudine | Lagarde, Valérie | Pasquet, Jean-Max | Reiffers, Josy | Garbay, Bertrand | Mahon, François-Xavier^; | Turcq, Béatrice

Affiliations: Laboratoire Hématopoïèse Leucémique et Cibles Thérapeutiques, INSERM U876, Université Victor Segalen Bordeaux 2, Bordeaux, France | Institut Bergonié, Centre Régional de Lutte Contre le Cancer de Bordeaux et du Sud-Ouest, Bordeaux, France | Université de Bordeaux, IPB, EA 4135, ENSTBB, Bordeaux, France | Laboratoire Hématologie, Hôpital Haut-Lévêque, CHU de Bordeaux, Bordeaux, France

Note: [] Corresponding author: Béatrice Turcq, Ph.D., Laboratoire Hématopoïèse Leucémique et Cibles Thérapeutiques, Inserm U876, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. Tel.: +33 557 571 051; Fax: +33 556 938 883; E-mail: beatrice.turcq@u-bordeaux2.fr

Abstract: Objective: Imatinib mesylate is a tyrosine kinase inhibitor used as first line treatment in chronic myeloid leukaemia. Despite a remarkable effectiveness, treatment failure cases have been reported in 20 percent of CML patients. The identification of biomarkers which can predict the response to imatinib is our point of interest. Methods: Gene expression profiling microarray was carried out on secondary imatinib resistant patients. Longitudinal studies were performed on imatinib treated responder/resistant patients. Then, Q-RT/PCR studies were realized on patients prior imatinib initiation. Results: For imatinib responder patients, we observed a strong and lasting decrease of α-defensin 1-3 and α-defensin 4 expression. For relapse patients, we observed a dramatic increase of α-defensin 1-3 and α-defensin 4 expression before BCR-ABL transcript increase. Moreover, before imatinib initiation, α-defensin 1-3 and α-defensin 4 expression was significantly lower in the resistant group than in the responder group. Conclusion: The variation of expression of α-defensin 1-3 and α-defensin 4 in peripheral blood is associated with imatinib resistance and may reflect an adequate immune control of the disease. Monitoring of α-defensin 1-3 and α-defensin 4 could be helpful to predict the patients who are not going to respond to the treatment.

Keywords: Chronic myeloid leukaemia, imatinib resistance, α-defensin, predictive biomarker

DOI: 10.3233/DMA-2011-0777

Journal: Disease Markers, vol. 30, no. 5, pp. 221-227, 2011